The present invention relates to a pharmaceutical composition which has the increased solubility of a triptan compound by using saccharin.
A triptan compound is an agonist selective for serotonin, acts on 5-HT1B1D to constrict expanded blood vessels, and may be used for migraines with aura or sudden severe migraines without aura.
In general, the triptan compound is orally administered and taken, and usually administered in the form of a tablet or a capsule, and in recent years, development has been conducted to administer the triptan compound as an orally disintegration tablet (ODT), an orally disintegration film (ODF) or a nasal formulation capable of being easily administered to patients, children, or the aged, which have difficulty in swallowing the tablet or the capsule, without water.
Zolmitriptan is a triptan-based compound (hereinafter, referred to as a triptan compound), the chemical name thereof is (S)-4-{{3-[2-(dimethylaminoethyl)]-1H-indol-5-1}methyl}-2-oxazolidinone, the solubility thereof to water is 1.3 mg/ml (25° C.), and the bioavailability thereof is about 40% when administered to the oral cavity and the nasal cavity.
Zolmitriptan is a tablet and may be administered in an amount of up to 10 mg a day, and a tablet (Zomig, AstraZeneca, United Kingdom) and an orally disintegration tablet (Zomig ZMT, AstraZeneca, United Kingdom) have been developed in 2 mg and 5 mg dosage forms.
Saccharin is a generally recognized as safe (GRAS) material, and is known to be 500 times or more sweeter than sugar. Saccharin is variously used as a food additive or a pharmaceutical additive. Further, saccharin acts as a co-former in the co-crystal technology, and has been reported to be capable of increasing the solubility of a drug due to the interaction with indomethacin and carbamazepine.
Patent Document 1 describes that zolmitriptan was dissolved in an acidic medium to prepare zolmitriptan into a dosage form suitable for nasal administration in the form of a salt, but there was inconvenience in that a phosphate should be further added thereto in order to adjust the acidic zolmitriptan salt to a desired pH.